Proteins that control key cellular processes, such as tumor suppressors and cyclins, commonly turn over rapidly, a property that facilitates prompt adjustments in their levels. The enzyme ornithine decarboxylase (ODC) is encoded by an early-response gene and its over-expression can transform cells. Drugs that target ODC are in clinical trial as cancer- therapeutic and-preventative agents. The degradation rate of mammalian ODC is tightly controlled; in particular, polyamines, the downstream product of ODC, induce its degradation. The mechanisms that underlie this are becoming better understood and involve interaction Of ODC with a polyamine-induced protein, which catalyzes degradation by the proteasome. Similar mechanisms are likely to act to control ODC in the budding yeast S. cervisiae, but have been little explored. To elucidate the process of regulation I will: (1) Isolate mutants that impede regulation. (2) Identify and characterize the function of proteins that directly interact with ODC. It is anticipated that these studies will elucidate degradative mechanisms shared by yeast and mammalian cells.